Journal of the American Society of Nephrology
2007 JASN IMPACT FACTOR 7.111 HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP 
    advanced
CURRENT ISSUE ARCHIVES JASN Express ONLINE SUBMISSION


This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Morigi, M.
Right arrow Articles by Remuzzi, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Morigi, M.
Right arrow Articles by Remuzzi, G.
J Am Soc Nephrol 15:1794-1804, 2004
© 2004 American Society of Nephrology

BASIC SCIENCE

Mesenchymal Stem Cells Are Renotropic, Helping to Repair the Kidney and Improve Function in Acute Renal Failure

Marina Morigi*, Barbara Imberti*, Carla Zoja*, Daniela Corna*, Susanna Tomasoni*, Mauro Abbate*, Daniela Rottoli*, Stefania Angioletti*, Ariela Benigni*, Norberto Perico*, Malcolm Alison{dagger} and Giuseppe Remuzzi*,{ddagger}

*Mario Negri Institute for Pharmacological Research, Bergamo, Italy; {dagger}Department of Histopathology, Imperial College London, Hammersmith Hospital, London, United Kingdom; and {ddagger}Unit of Nephrology and Dialysis, Azienda Ospedaliera, Ospedali Riuniti di Bergamo, Bergamo, Italy

Correspondence to Dr. Marina Morigi, "Mario Negri" Institute for Pharmacological Research, Via Gavazzeni 11, 24125 Bergamo, Italy. Phone: +39-035-319-888; Fax: +39-035-319-331; E-mail: morigi{at}marionegri.it

ABSTRACT. Injury to a target organ can be sensed by bone marrow stem cells that migrate to the site of damage, undergo differentiation, and promote structural and functional repair. This remarkable stem cell capacity prompted an investigation of the potential of mesenchymal and hematopoietic stem cells to cure acute renal failure. The model of renal injury induced in mice by the anticancer agent cisplatin was chosen. Injection of mesenchymal stem cells of male bone marrow origin remarkably protected cisplatin-treated syngeneic female mice from renal function impairment and severe tubular injury. Y chromosome–containing cells localized in the context of the tubular epithelial lining and displayed binding sites for Lens culinaris lectin, indicating that mesenchymal stem cells engraft the damaged kidney and differentiate into tubular epithelial cells, thereby restoring renal structure and function. Mesenchymal stem cells markedly accelerated tubular proliferation in response to cisplatin-induced damage, as revealed by higher numbers of Ki-67–positive cells within the tubuli with respect to cisplatin-treated mice that were given saline. Hematopoietic stem cells failed to exert beneficial effects. These results offer a strong case for exploring the possibility that mesenchymal stem cells by virtue of their renotropic property and tubular regenerative potential may have a role in the treatment of acute renal failure in humans.




This article has been cited by other articles:


Home page
 Nephrol Dial TransplantHome page
D. Vansthertem, N. Caron, A.-E. Decleves, S. Cludts, A. Gossiaux, D. Nonclercq, B. Flamion, A. Legrand, and G. Toubeau
Label-retaining cells and tubular regeneration in postischaemic kidney
Nephrol. Dial. Transplant., December 1, 2008; 23(12): 3786 - 3797.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
B. Bi, J. Guo, A. Marlier, S. R. Lin, and L. G. Cantley
Erythropoietin expands a stromal cell population that can mediate renoprotection
Am J Physiol Renal Physiol, October 1, 2008; 295(4): F1017 - F1022.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
F. Casiraghi, N. Azzollini, P. Cassis, B. Imberti, M. Morigi, D. Cugini, R. A. Cavinato, M. Todeschini, S. Solini, A. Sonzogni, et al.
Pretransplant Infusion of Mesenchymal Stem Cells Prolongs the Survival of a Semiallogeneic Heart Transplant through the Generation of Regulatory T Cells
J. Immunol., September 15, 2008; 181(6): 3933 - 3946.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
M. Morigi, M. Introna, B. Imberti, D. Corna, M. Abbate, C. Rota, D. Rottoli, A. Benigni, N. Perico, C. Zoja, et al.
Human Bone Marrow Mesenchymal Stem Cells Accelerate Recovery of Acute Renal Injury and Prolong Survival in Mice
Stem Cells, August 1, 2008; 26(8): 2075 - 2082.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
R. Abdi, P. Fiorina, C. N. Adra, M. Atkinson, and M. H. Sayegh
Immunomodulation by Mesenchymal Stem Cells: A Potential Therapeutic Strategy for Type 1 Diabetes
Diabetes, July 1, 2008; 57(7): 1759 - 1767.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
C. Mias, E. Trouche, M.-H. Seguelas, F. Calcagno, F. Dignat-George, F. Sabatier, M.-D. Piercecchi-Marti, L. Daniel, P. Bianchi, D. Calise, et al.
Ex Vivo Pretreatment with Melatonin Improves Survival, Proangiogenic/Mitogenic Activity, and Efficiency of Mesenchymal Stem Cells Injected into Ischemic Kidney
Stem Cells, July 1, 2008; 26(7): 1749 - 1757.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
F. Togel, Y. Yang, P. Zhang, Z. Hu, and C. Westenfelder
Bioluminescence imaging to monitor the in vivo distribution of administered mesenchymal stem cells in acute kidney injury
Am J Physiol Renal Physiol, July 1, 2008; 295(1): F315 - F321.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
N. Shimony, I. Avrahami, R. Gorodetsky, G. Elkin, K. Tzukert, L. Zangi, L. Levdansky, L. Krasny, and Y. S. Haviv
A 3D rotary renal and mesenchymal stem cell culture model unveils cell death mechanisms induced by matrix deficiency and low shear stress
Nephrol. Dial. Transplant., June 1, 2008; 23(6): 2071 - 2080.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
R. Schmitt and L. G. Cantley
The impact of aging on kidney repair
Am J Physiol Renal Physiol, June 1, 2008; 294(6): F1265 - F1272.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
B. Mazzinghi, E. Ronconi, E. Lazzeri, C. Sagrinati, L. Ballerini, M. L. Angelotti, E. Parente, R. Mancina, G. S. Netti, F. Becherucci, et al.
Essential but differential role for CXCR4 and CXCR7 in the therapeutic homingof human renal progenitor cells
J. Exp. Med., February 18, 2008; 205(2): 479 - 490.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
G. Stokman, J. C. Leemans, I. Stroo, I. Hoedemaeker, N. Claessen, G. J. D. Teske, J. J. Weening, and S. Florquin
Enhanced mobilization of bone marrow cells does not ameliorate renal fibrosis
Nephrol. Dial. Transplant., February 1, 2008; 23(2): 483 - 491.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
A. Vogetseder, N. Picard, A. Gaspert, M. Walch, B. Kaissling, and M. Le Hir
Proliferation capacity of the renal proximal tubule involves the bulk of differentiated epithelial cells
Am J Physiol Cell Physiol, January 1, 2008; 294(1): C22 - C28.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. H. Klopp, E. L. Spaeth, J. L. Dembinski, W. A. Woodward, A. Munshi, R. E. Meyn, J. D. Cox, M. Andreeff, and F. C. Marini
Tumor Irradiation Increases the Recruitment of Circulating Mesenchymal Stem Cells into the Tumor Microenvironment
Cancer Res., December 15, 2007; 67(24): 11687 - 11695.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
E. Lazzeri, C. Crescioli, E. Ronconi, B. Mazzinghi, C. Sagrinati, G. S. Netti, M. L. Angelotti, E. Parente, L. Ballerini, L. Cosmi, et al.
Regenerative Potential of Embryonic Renal Multipotent Progenitors in Acute Renal Failure
J. Am. Soc. Nephrol., December 1, 2007; 18(12): 3128 - 3138.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
L. Li, P. Truong, P. Igarashi, and F. Lin
Renal and Bone Marrow Cells Fuse after Renal Ischemic Injury
J. Am. Soc. Nephrol., December 1, 2007; 18(12): 3067 - 3077.
[Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
B. Imberti, M. Morigi, S. Tomasoni, C. Rota, D. Corna, L. Longaretti, D. Rottoli, F. Valsecchi, A. Benigni, J. Wang, et al.
Insulin-Like Growth Factor-1 Sustains Stem Cell Mediated Renal Repair
J. Am. Soc. Nephrol., November 1, 2007; 18(11): 2921 - 2928.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
D. G. Phinney and D. J. Prockop
Concise Review: Mesenchymal Stem/Multipotent Stromal Cells: The State of Transdifferentiation and Modes of Tissue Repair Current Views
Stem Cells, November 1, 2007; 25(11): 2896 - 2902.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
B. Bi, R. Schmitt, M. Israilova, H. Nishio, and L. G. Cantley
Stromal Cells Protect against Acute Tubular Injury via an Endocrine Effect
J. Am. Soc. Nephrol., September 1, 2007; 18(9): 2486 - 2496.
[Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
E. Imai and H. Iwatani
The Continuing Story of Renal Repair with Stem Cells
J. Am. Soc. Nephrol., September 1, 2007; 18(9): 2423 - 2424.
[Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
U. Kunter, S. Rong, P. Boor, F. Eitner, G. Muller-Newen, Z. Djuric, C. R. van Roeyen, A. Konieczny, T. Ostendorf, L. Villa, et al.
Mesenchymal Stem Cells Prevent Progressive Experimental Renal Failure but Maldifferentiate into Glomerular Adipocytes
J. Am. Soc. Nephrol., June 1, 2007; 18(6): 1754 - 1764.
[Abstract] [Full Text] [PDF]

Home page
 haematolHome page
A. De Becker, P. Van Hummelen, M. Bakkus, I. Vande Broek, J. De Wever, M. De Waele, and I. Van Riet
Migration of culture-expanded human mesenchymal stem cells through bone marrow endothelium is regulated by matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-3
Haematologica, April 1, 2007; 92(4): 440 - 449.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
J. Li, J. A. Deane, N. V. Campanale, J. F. Bertram, and S. D. Ricardo
The Contribution of Bone Marrow-Derived Cells to the Development of Renal Interstitial Fibrosis
Stem Cells, March 1, 2007; 25(3): 697 - 706.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
A. Vogetseder, T. Palan, D. Bacic, B. Kaissling, and M. Le Hir
Proximal tubular epithelial cells are generated by division of differentiated cells in the healthy kidney
Am J Physiol Cell Physiol, February 1, 2007; 292(2): C807 - C813.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
M. Broekema, M. C. Harmsen, M. J.A. van Luyn, J. A. Koerts, A. H. Petersen, T. G. van Kooten, H. van Goor, G. Navis, and E. R. Popa
Bone Marrow-Derived Myofibroblasts Contribute to the Renal Interstitial Myofibroblast Population and Produce Procollagen I after Ischemia/Reperfusion in Rats
J. Am. Soc. Nephrol., January 1, 2007; 18(1): 165 - 175.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
R. Poulsom, E. I. Prodromidi, C. D. Pusey, and H. T. Cook
Cell therapy for renal regeneration--time for some joined-up thinking?
Nephrol. Dial. Transplant., December 1, 2006; 21(12): 3349 - 3353.
[Full Text] [PDF]

Home page
 Stem CellsHome page
E. I. Prodromidi, R. Poulsom, R. Jeffery, C. A. Roufosse, P. J. Pollard, C. D. Pusey, and H. T. Cook
Bone Marrow-Derived Cells Contribute to Podocyte Regeneration and Amelioration of Renal Disease in a Mouse Model of Alport Syndrome
Stem Cells, November 1, 2006; 24(11): 2448 - 2455.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
M. H. Little
Regrow or Repair: Potential Regenerative Therapies for the Kidney
J. Am. Soc. Nephrol., September 1, 2006; 17(9): 2390 - 2401.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
C. Sagrinati, G. S. Netti, B. Mazzinghi, E. Lazzeri, F. Liotta, F. Frosali, E. Ronconi, C. Meini, M. Gacci, R. Squecco, et al.
Isolation and Characterization of Multipotent Progenitor Cells from the Bowman's Capsule of Adult Human Kidneys
J. Am. Soc. Nephrol., September 1, 2006; 17(9): 2443 - 2456.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
U. Kunter, S. Rong, Z. Djuric, P. Boor, G. Muller-Newen, D. Yu, and J. Floege
Transplanted Mesenchymal Stem Cells Accelerate Glomerular Healing in Experimental Glomerulonephritis
J. Am. Soc. Nephrol., August 1, 2006; 17(8): 2202 - 2212.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
S.-I. Inoue, K. Ishikawa, K. Nakada, A. Sato, H. Miyoshi, and J.-I. Hayashi
Suppression of disease phenotypes of adult mito-mice carrying pathogenic mtDNA by bone marrow transplantation
Hum. Mol. Genet., June 1, 2006; 15(11): 1801 - 1807.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
P. Devarajan
Update on Mechanisms of Ischemic Acute Kidney Injury
J. Am. Soc. Nephrol., June 1, 2006; 17(6): 1503 - 1520.
[Full Text] [PDF]

Home page
 Stem CellsHome page
B. Dekel, E. Shezen, S. Even-Tov-Friedman, H. Katchman, R. Margalit, A. Nagler, and Y. Reisner
Transplantation of Human Hematopoietic Stem Cells into Ischemic and Growing Kidneys Suggests a Role in Vasculogenesis but Not Tubulogenesis
Stem Cells, May 1, 2006; 24(5): 1185 - 1193.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
T. Yokoo, A. Fukui, T. Ohashi, Y. Miyazaki, Y. Utsunomiya, T. Kawamura, T. Hosoya, M. Okabe, and E. Kobayashi
Xenobiotic Kidney Organogenesis from Human Mesenchymal Stem Cells Using a Growing Rodent Embryo
J. Am. Soc. Nephrol., April 1, 2006; 17(4): 1026 - 1034.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
G. Zerbini, L. Piemonti, A. Maestroni, G. Dell'Antonio, and G. Bianchi
Stem Cells and the Kidney: A New Therapeutic Tool?
J. Am. Soc. Nephrol., April 1, 2006; 17(4_suppl_2): S123 - S126.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
J. D. Raman, N. P. Mongan, L. Liu, S. K. Tickoo, D. M. Nanus, D. S. Scherr, and L. J. Gudas
Decreased expression of the human stem cell marker, Rex-1 (zfp-42), in renal cell carcinoma
Carcinogenesis, March 1, 2006; 27(3): 499 - 507.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
C. Roufosse, G. Bou-Gharios, E. Prodromidi, C. Alexakis, R. Jeffery, S. Khan, W. R. Otto, J. Alter, R. Poulsom, and H. T. Cook
Bone Marrow-Derived Cells Do Not Contribute Significantly to Collagen I Synthesis in a Murine Model of Renal Fibrosis
J. Am. Soc. Nephrol., March 1, 2006; 17(3): 775 - 782.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
J.-K. Guo, A. Schedl, and D. S. Krause
Bone Marrow Transplantation Can Attenuate the Progression of Mesangial Sclerosis
Stem Cells, February 1, 2006; 24(2): 406 - 415.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
D. R. Abrahamson and B. M. Steenhard
Renal Therapy by Stem Cells: Outsource or In-House?
J. Am. Soc. Nephrol., January 1, 2006; 17(1): 12 - 14.
[Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
D. Kim and G. R. Dressler
Nephrogenic Factors Promote Differentiation of Mouse Embryonic Stem Cells into Renal Epithelia
J. Am. Soc. Nephrol., December 1, 2005; 16(12): 3527 - 3534.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
M. E. De Broe
Tubular regeneration and the role of bone marrow cells: 'stem cell therapy' - a panacea?
Nephrol. Dial. Transplant., November 1, 2005; 20(11): 2318 - 2320.
[Full Text] [PDF]

Home page
 BloodHome page
V. Sordi, M. L. Malosio, F. Marchesi, A. Mercalli, R. Melzi, T. Giordano, N. Belmonte, G. Ferrari, B. E. Leone, F. Bertuzzi, et al.
Bone marrow mesenchymal stem cells express a restricted set of functionally active chemokine receptors capable of promoting migration to pancreatic islets
Blood, July 15, 2005; 106(2): 419 - 427.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
H. Rabb
Paracrine and differentiation mechanisms underlying stem cell therapy for the damaged kidney
Am J Physiol Renal Physiol, July 1, 2005; 289(1): F29 - F30.
[Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
F. Togel, Z. Hu, K. Weiss, J. Isaac, C. Lange, and C. Westenfelder
Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms
Am J Physiol Renal Physiol, July 1, 2005; 289(1): F31 - F42.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
B. M. Steenhard, K. S. Isom, P. Cazcarro, J. H. Dunmore, A. R. Godwin, P. L. St. John, and D. R. Abrahamson
Integration of Embryonic Stem Cells in Metanephric Kidney Organ Culture
J. Am. Soc. Nephrol., June 1, 2005; 16(6): 1623 - 1631.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
F. Togel, Z. Hu, K. Weiss, J. Isaac, C. Lange, C. Westenfelder, T. Stasko, M.D. Brown, J.A. Carucci, S. Euvrard, et al.
Amelioration of Acute Renal Failure by Stem Cell Therapy--Paracrine Secretion Versus Transdifferentiation into Resident Cells: Administered Mesenchymal Stem Cells Protect against Ischemic Acute Renal Failure through Differentiation-Independent Mechanisms. Am J Physiol Renal Physiol E-pub February 15, 2005
J. Am. Soc. Nephrol., May 1, 2005; 16(5): 1153 - 1163.
[Full Text] [PDF]


HOME CURRENT ISSUE ARCHIVES JASN Express ONLINE SUBMISSION AUTHOR INFO
EDITORIAL BOARD SUBSCRIBE FEEDBACK ALERTS HELP

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673